Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization

• Published in: NeuroImage (Orlando, Fla.) Vol. 279; p. 120325
• Main Authors: Lin, Siying, Zhang, Haoyang, Qi, Mengling, Cooper, David N., Yang, Yuedong, Yang, Yuanhao, Zhao, Huiying
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2023; Elsevier Limited; Elsevier
• Subjects: Alzheimer's disease; Amyotrophic lateral sclerosis; Angina pectoris; Autism; Biomarkers; Brain disorders; Brain imaging-derived phenotypes; Cardiovascular disease; Cardiovascular diseases; Causal relationships; Consortia; Genetic correlation; Genetic relationship; Genome-wide association studies; Genomes; Genomic analysis; Genomics; Hypertension; Insomnia; Magnetic resonance imaging; Medical imaging; Mental depression; Mental disorders; Neuroimaging; Neurological disorders; Phenotypes; Schizophrenia; Single-nucleotide polymorphism; Sleep; Statistical analysis; Statistics; Temporal lobe; PP; ADHD; GWAS; Brain disorders; Genetic correlation; ALS; WTE; IVW; SCZ; MDD; STM; SA; TFA; INS; STR; ASD; HBP; KEGG; BID; MAGMA; MI; CA; AD; CH; MR; MS; GO; LDSC; AN; UKB; AP; PTSD; PAD; MAF; PD; rg; Brain imaging-derived phenotypes; Cardiovascular diseases; Causal relationships; HF; NAR; EPI
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2023.120325

•We found the first evidence for significant putative causal effects of multiple brain region-specific IDPs on the increased risks of ALS, MDD, ASD, and SCZ.•The brain IDPs from temporal lobe were identified as a putatively causal consequence of hypertension.•We identified causal SNPs, rs853676, rs199456 and rs7969401 to be associated with MDD, ASD, SCZ, and multiple brain IDPs.•We identified a list of candidate genes simultaneously associated with brain disorders, cardiovascular diseases and brain IDPs from multiple brain regions. Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases.